8om1
Mitochondrial complex I from Mus musculus in the active stateMitochondrial complex I from Mus musculus in the active state
Structural highlights
FunctionNU5M_MOUSE Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) that is believed to belong to the minimal assembly required for catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (By similarity). Publication Abstract from PubMedRespiratory complex I, a key enzyme in mammalian metabolism, captures the energy released by reduction of ubiquinone by NADH to drive protons across the inner mitochondrial membrane, generating the proton-motive force for ATP synthesis. Despite remarkable advances in structural knowledge of this complicated membrane-bound enzyme, its mechanism of catalysis remains controversial. In particular, how ubiquinone reduction is coupled to proton pumping and the pathways and mechanisms of proton translocation are contested. We present a 2.4-A resolution cryo-EM structure of complex I from mouse heart mitochondria in the closed, active (ready-to-go) resting state, with 2945 water molecules modeled. By analyzing the networks of charged and polar residues and water molecules present, we evaluate candidate pathways for proton transfer through the enzyme, for the chemical protons for ubiquinone reduction, and for the protons transported across the membrane. Last, we compare our data to the predictions of extant mechanistic models, and identify key questions to answer in future work to test them. Investigation of hydrated channels and proton pathways in a high-resolution cryo-EM structure of mammalian complex I.,Grba DN, Chung I, Bridges HR, Agip AA, Hirst J Sci Adv. 2023 Aug 2;9(31):eadi1359. doi: 10.1126/sciadv.adi1359. Epub 2023 Aug 2. PMID:37531432[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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